The invention relates to an improved process for the isolation of phenyl ester salts from mixtures comprising sulfolane (tetrahydrothiophene-1,1-dioxide), such as a crude reaction mixture in which a phenyl ester salt is synthesized.
Phenyl ester salts, as known in the art, have been used in detergents and as bleach activators for fabric laundering and cleaning applications. The synthesis, isolation, and purification of phenyl ester salts which are used as bleach activators, is described in U.S. Pat. Nos. 5,717,188, 5,650,527 and 5,523,434. The isolation of these phenyl ester salts is typically by techniques such as filtration or centrifugation.
In most cases, the isolation or separation steps must be done at low temperatures in order to minimize or avoid unacceptable losses of product. Centrifugation is usually done at temperatures below about 100xc2x0 C. In fact, equipment rated for use above about 100xc2x0 C. is difficult to obtain. However, by collecting the product at temperatures lower than about 100xc2x0 C., several problems are encountered. For instance, allowing the mixture to cool to temperatures below 100xc2x0 C. or to ambient temperature as described in the art, is not a satisfactory method for the isolation of many phenyl ester salts. Although filtration or centrifugation at these temperatures may be possible, the process is often too slow to be economical for large scale production. At typical reaction concentrations, the mixture becomes almost solid and cannot be readily moved for isolation. While the mixture may be made more tractable by dilution with a solvent, the result is loss of product due to increased solubility as well as a large downstream flow of solvent, which must be purified and recovered.
Another approach used to isolate detergents and bleach activators is to remove the solvent by vacuum distillation at temperatures up to 200xc2x0 C. This approach is usually unsatisfactory for several reasons. Particularly for large scale production, the evaporation of the reaction solvent is expensive. Further, impurities present in the reaction mixture remain with the product, and must be removed in subsequent steps. In addition, degradation of the solvent and reaction components at the high temperatures required for drying imparts undesired color and impurities to the product. When the phenyl ester salts are made in a reaction mixture comprising sulfolane as the solvent, the degradation of the solvent is a particular problem at elevated temperatures.
Another problem associated with the isolation of phenyl ester salts from reaction mixtures occurs when the product is in the form of very fine crystals. These fine crystals rapidly form a layer upon the filter medium that is virtually impervious to the penetration of liquid, thus blinding the filter or centrifuge. When the mother liquid is viscous, these types of crystals do not settle well on sedimentation style devices. Separation is problematic when the density of the solid and the reaction solvent are similar. Slurries of fine crystals are also difficult to pump or transfer from one vessel to another at typical reaction concentrations and low temperatures.
Patents that describe techniques for the isolation of phenyl ester salts using filtration or centrifugation are discussed below, however, these techniques are typically carried out at temperatures of less than 100xc2x0 C. The abstract of Japanese Patent Number 8,245,549 describes the isolation of a sulfonate from a solvent having a boiling point of less than 100xc2x0 C. by centrifugation. The Abstract of Japanese Patent No. 58,157,760 describes the preparation of m-xylene-4-sulfonic acid in which centrifugation is used in product recovery after crystallization. Japanese Patent No. 4,103,567 describes the separation of alkoxybenzene sulphonic acid salts, such as sodium 5-chloro-2-(2-methoxyethoxy) benzenesulfonate, in which the product is recovered by centrifugation. The Abstract of East German Patent DD 295, 349 describes the production of basic phenolate-containing calcium sulfonates, which involves centrifuging or filtering to remove solid oil-insoluble components. U.S. Pat. No. 5,429,773 relates to the centrifugation or isolation of an alkyl ester sulfonate surfactant composition at a temperature of 10-43xc2x0 C. U.S. Pat. No. 5,523,434 teaches a process for manufacture of phenol sulfonate esters of N-nonanoyl-6-aminocaproic acid, which includes centrifugation at low temperatures for isolation. U.S. Pat. No. 5,650,527 describes a method of isolation wherein the reaction solvent is removed by either evaporation, or crystallization followed by filtration.
Accordingly, what is needed is a process for the isolation of phenyl ester salts from reaction mixtures comprising sulfolane which avoids the following: high temperatures, excessive dilution with cosolvent, excessive problems with pumping or transferring the mixture, blinding of the filter medium, and undesirable solvent interactions. The invention described below answers this need.
The invention discloses an improved process for the isolation of a phenyl ester salt directly from a mixture comprising sulfolane (tetrahydrothiophene-1,1-dioxide). For example, the invention relates to the improved isolation of a phenyl ester salt from the crude reaction mixture in which the phenyl ester salt is synthesized. Any of the following steps, taken alone or in combination will improve the isolation of a phenyl ester salt from a mixture comprising sulfolane: (i) centrifugation or filtration within an optimal temperature range of about 110-150xc2x0 C., (ii) addition of a solvent in amounts of about 2-4% based on weight of the crude reaction mixture to reduce the viscosity and/or density of the mother liquid prior to filtration or centrifugation, and (iii) slow cooling of the crude reaction mixture at a rate of about 8-10xc2x0 C. per hour. Advantageously, the invention avoids excessive dilution with sulfolane, excessive problems with pumping the mixture, problems related to viscosity and/or density, blinding of the filter medium, or addition of large amounts of a cosolvent.
Additionally, this invention is an improvement over the practice of filtering or centrifuging at high temperatures of above 150xc2x0 C., where these higher temperatures result in less complete separation of the phenyl ester salt from the solvent due to the increased solubility at that temperature. This loss of product often leads to the recycling of the filtrate or centrate with concomitant loss of efficiency, loss of product, and loss of product quality.
In a particularly preferred embodiment, this invention is used to isolate sodium 4-sulfophenyl 6-[(1-oxynonyl)-amino]hexanoate, sodium 4-(nonanoyloxy) benzenesulfonate, or sodium benzoyloxy benzenesulphonate, which are phenyl ester salts used as bleach activators.
Additional objects and advantages of the invention are discussed in the detailed description that follows, and will be obvious from that description, or may be learned by practice of the invention. It is to be understood that both this summary and the following detailed description are exemplary and explanatory only and are not intended to restrict the invention.
This invention relates to a process for the isolation of a phenyl ester salt from a mixture comprising sulfolane (tetrahydrothiophene-1,1-dioxide), such as a crude reaction mixture in which a phenyl ester salt is synthesized.
Phenyl ester salts are used as bleach activators in laundry detergents and other cleaning formulations. As shown in the reaction scheme below, the phenyl ester salt is hydrolyzed upon nucleophilic attack by a perhydroxide anion to yield a peroxy acid that acts as a bleaching agent, and a substituted phenolic anion. 
To be effective as a bleach activator, the phenyl ester salt must readily react with a perhydroxide anion to produce (activate) the corresponding peroxyacid within the length of time and at the temperature of a typical wash cycle. Employing the process of the invention improves the perhydrolysis rate of phenyl ester salts. Advantageously, then, this invention improves the efficacy of the detergent containing a phenyl ester salt bleach activator. The process of the invention can be used with any phenyl ester salt.
Exemplary phenyl ester salts, which are used as bleach activators, are described in U.S. Pat. Nos. 4,634,551; 4,852,989; 5,391,780; 5,393,905; 5,393,901; 5,414,099; 5,466,840; 5,523,434; 5,650,527; and 5,717,118; as well as in published PCT applications WO 94/18159, WO 95/07883, WO 96/16148, and WO 99/09004. These U.S. Patents and published PCT applications are incorporated herein in their entirety.
Examples of phenyl ester salts which may be isolated and recovered using the process of this invention include compounds described by formula (I) or (II) below: 
R1 is selected from C1-C22 alkyl, C2-C22 alkenyl, C2-C22 alkynyl, C3-C22 cycloalkyl, and C6-C14 aryl. Preferably, R1 is selected from C6-C10 alkyl, and C6-C10 aryl.
R2 and R5 are each independently selected from hydrogen, C1-C22 alkyl, C2-C22 alkenyl, C2-C22 alkynyl, C3-C22 cycloalkyl, and C6-C14 aryl. Alternatively, in formula II, R2 and R5, together with the nitrogen carrying them, form a C3-C10 heterocycle. This heterocycle may or may not contain additional heteroatoms selected from: nitrogen, oxygen, sulfur, and phosphorous. Preferably, R2 is hydrogen, and R5 is selected from hydrogen, C6-C10 alkyl, and C6-C10 aryl.
R3 and R4 are each independently selected in each instance from hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, and C6-C10 aryl. The R3 and R4 groups, together with the carbon carrying them, may form a C3-C1 cycloalkyl group. This cycloalkyl group may or may not contain heteroatoms selected from: nitrogen, oxygen, sulfur, and phosphorous. Preferably, R3 and R4 are independently selected in each instance from hydrogen and methyl.
The substituent Y on the phenyl ring is selected from SO3xe2x88x92M+, CO2xe2x88x92M+, SO4xe2x88x92M+, and N+(R7)3Xxe2x88x92. M represents a cation, and may be selected from hydrogen, ammonium and alkali metal atom. R7 in each instance is independently a C1-C4 alkyl group. X is an anion, and may be selected from a halide, hydroxide, methylsulfate, or acetate ion. Preferably, Y is selected from SO3xe2x88x92M+, and CO2xe2x88x92M+; where M is a sodium ion.
The phenyl ring may also be further substituted with 1 to 4 other substituents. The substituents may be electron-withdrawing or electron-donating groups. The substituents may, for example, be chosen to adjust the perhydrolysis rate, to adjust the hydrophilic/hydrophobic nature of the phenyl ester salt, or to adjust the solubility of the phenyl ester salt. Possible groups include, but are not limited to, hydroxyl, halogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, and C1-C10 alkoxy, and amino groups. When the phenyl ester salts are to be used as bleach activators, it is also desirable to have electron-withdrawing groups on the phenyl ring, to facilitate nucleophilic attack by a perhydroxide anion. In general, a substituted phenol is the preferred leaving group, however there may be other acceptable leaving groups, as will be evident to one of ordinary skill in the art. The substituted phenyl group should be sufficiently reactive for the reaction to occur within an optimum time frame, such as a wash cycle. The leaving group should also be sufficiently stable to ensure that the rate of back reaction will be negligible. However, the substituted phenyl group should not be too reactive, as this may lead to storage and stability problems in a bleaching or detergent formulation.
The value of xe2x80x9cmxe2x80x9d is 0 or 1 and represents the presence or absence of an amido group in the compound. Acceptable values for xe2x80x9cnxe2x80x9d may range from about 0 to 20, and preferred values for xe2x80x9cnxe2x80x9d include from about 0 to about 6.
The bleaching effectiveness of the resulting peroxy acid resulting from the phenyl ester salt may be related to its hydrophilic/hyprophobic balance. This balance, related to the choice of xe2x80x9cmxe2x80x9d and particularly xe2x80x9cnxe2x80x9d, affects the solubility of the peroxy acid in water. In addition, the hydrophilic/hydrophobic balance determines which types of stains and soils that the molecule will bleach most efficiently. The presence of an amido group in the phenyl ester salt may impart certain desirable features to a bleach activator, as described in U.S. Pat. No. 4,852,989. For example, in certain circumstances, the presence of an amido group has been found to lower the vapor pressure and/or increase the melting point of the resulting peroxyacid thereby increasing the stability of the peroxyacid. Additionally, it is generally preferred to choose the value of xe2x80x9cnxe2x80x9d and various substituents to increase the water solubility of the peroxyacid.
For the various substituents of the phenyl ester salts of formula (I) or (II), the alkyl, alkenyl, and alkynyl groups may be straight or branched. The alkyl, alkenyl, and alkynyl groups may be optionally substituted with halogen, alkoxy groups, or water-solubilizing groups. In addition, these groups may also be substituted with various steroids, natural products and fatty acids, as known in the art.
A xe2x80x9cwater-solubilizing groupxe2x80x9d is a substituent that increases the solubility of a compound in aqueous solution. Exemplary water-solubilizing groups include, but are not limited to, quaternary amine, sulfate, sulfonate, carboxylate, phosphate, phosphonate, polyether, polyhydroxyl, boronate, and amide groups such as xe2x80x94CONH2 and CONHCH3. The water solubilizing groups may also include sulfo, sulfonamido, carbonamido, sulfamoyl, carbamoyl, hydroxyl, and salts thereof.
The C2-C22 alkenyl and C3-C22 alkynyl groups represent straight or branched chain hydrocarbon radicals containing 2 to 22 carbons in the chain and which contains at least one of a carbonxe2x80x94carbon double bond and/or at least one of a carbonxe2x80x94carbon triple bond.
The C3-C22 cycloalkyl heterocycles and rings may contain more than one degree of unsaturation and may be unsubstituted or substituted. The heterocycles and cycloalkyl rings may be optionally substituted with halogen, alkoxy groups, or water-solubilizing groups. These rings may be monocyclic, bicyclic, or polycyclic. In addition, these cycloalkyl rings may or may not contain one or more heteroatoms in the ring. Acceptable heteroatoms are selected from: oxygen, nitrogen, sulfur and phosphorus.
The C6-C14 aryl ring may be monocyclic, bicyclic, or polycyclic. In addition, the aryl ring may contain one or more heteroatoms. Appropriate heteroatoms include oxygen, nitrogen, sulfur, and phosphorus. Both the C3-C22 cycloalkyl rings and C6-C14 aryl rings may be substituted with appropriate C1-C4 alkylaryl, hydroxy, C1-C4 alkanyloxy, halogen or water-solubilizing groups. The term xe2x80x9carylxe2x80x9d includes carbocyclic aryl groups containing up to fourteen carbons, e.g., phenyl and naphthyl. The term xe2x80x9carylxe2x80x9d also includes heterocyclic aryl groups such as a 5 or 6-membered heterocyclic aromatic ring. These heterocyclic aromatic rings may also contain other heteroatoms selected from: oxygen, nitrogen, sulphur, and phosphorous. These heterocyclic aryl rings may be optionally fused to one or two phenyl rings or another 5 or 6-membered heteroaryl ring. Examples of such ring systems include thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, oxadiazolyl, tetrazolyl, thiatriazolyl, oxatriazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, thiazinyl, oxazinyl, triazinyl, thiadiazinyl, oxadiazinyl, dithiazinyl, dioxazinyl, oxathiazinyl, tetrazinyl, thiatriazinyl, oxatriazinyl, dithiadiazinyl, imidazolinyl, dihydropyrimidyl, tetrahydropyrimidyl, tetrazolo-[1,5-b]pyridazinyl and purinyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, indolyl, and the like. The aryl groups may be substituted or unsubstituted as discussed above for the alkyl, alkenyl, and alkynyl groups.
In addition, the term xe2x80x9carylxe2x80x9d includes arylene groups. The term xe2x80x9carylenexe2x80x9d defines a divalent carbocyclic aryl hydrocarbon moiety containing up to fourteen carbons, e.g., o-, m- and p-phenylene, and those substituted with one or two groups selected from C1-C4-alkyl, C1-C4-alkoxy or halogen.
In a particularly preferred embodiment, the invention relates to phenyl ester salts such as sodium 4-sulfophenyl-6-[(1-oxynonyl)amino]hexanoate, sodium 4-(nonanoyloxy) benzenesulfonate, or sodium benzoyloxy benzenesulphonate.
The phenyl ester salt to be isolated may be from a reaction product mixture with the reaction solvent (or a portion thereof) removed. Or, the starting phenyl ester salt may be the product after drying. Preferred dryers are mechanically agitated dryers capable of handling viscous material such as a Porcupine dryer from Bethlehem Corporation, Easton, Pa. or a List dryer from List Corporation, Acton, Mass. Alternatively, the starting phenyl ester salt may have been previously worked up to remove unwanted impurities, reaction by-products, solvent, color bodies, etc. The synthesis of phenyl ester salts which may be used as bleach activators, is discussed in U.S. Pat. No. 4,634,551, 4,852,989, 5,393,905, 5,523,434, 5,650,527, and WO 94/18159, which are hereby incorporated in their entirety.
In a preferred method for synthesizing phenyl ester salts, sodium 4-hydroxybenzenesulfonate, acetic anhydride and a carboxylic acid are heated in the presence of one or more catalysts to temperatures of about 155-175xc2x0 C., in sulfolane as the reaction solvent. Allowing the crude reaction mixture to cool to temperatures below 100xc2x0 C. or to ambient temperatures, is not a satisfactory method for isolation of the phenyl ester salt. Filtration at these lower temperatures is generally too slow to be economical for large scale production. In addition, at typical reaction concentrations, the mixture becomes almost solid and cannot be easily moved or transferred. Although the mixture may be made more tractable by diluting the mixture with a cosolvent, the disadvantages include loss of product due to solubility in the cosolvent and additional steps to recover and/or purify the solvent and cosolvent.
In an attempt to keep the mixture more manageable, filtration or centrifugation of the crude reaction mixture was attempted at temperatures above about 150xc2x0 C. Although at these higher temperatures, the rate of filtration was acceptable, the result was less complete isolation of the desired product from the sulfolane due to increased solubility of the phenyl ester salt at the higher temperatures. While centrate or filtrate containing the product may be recycled to improve the yield, the product quality deteriorates and the process becomes less efficient. Thus, it is important that as much product as possible be recovered in the first pass through the isolation device.
It has been found that the following processes, taken alone or in combination, improve the isolation of a phenyl ester salt from mixtures comprising sulfolane: (i) centrifugation or filtration at temperatures within an optimal range of about 110-150xc2x0 C., (ii) addition of a solvent in amounts of about 2-4% based on weight of the crude reaction mixture to reduce the viscosity and density of the mixture or slurry prior to filtration or centrifugation, and (iii) slow cooling of the crude reaction mixture, preferably at a rate of about 8-10xc2x0 C. per hour.
This invention covers a process for the isolation of a phenyl ester salt from a variety of mixtures comprising sulfolane. For example, if the phenyl ester salt is formed during the course of a reaction which uses sulfolane as the reaction solvent, then the mixture may be the slurry which is formed by cooling the crude reaction mixture to a temperature where the phenyl ester salt precipitates out of solution. Additionally, the mixture may comprise a phenyl ester salt and sulfolane during a re-crystallization step, wherein the phenyl ester salt is first dissolved at an elevated temperature, and then re-crystallized by adjusting the temperature to within a temperature range of about 110-120xc2x0 C.
In a preferred embodiment, the mixture is a crude reaction mixture. For instance, U.S. Pat. No. 5,650,527 describes a reaction wherein the phenyl ester salt is typically synthesized at temperatures between 155-175xc2x0 C. in sulfolane. According to the first step of the process described by this invention, the temperature of the crude reaction mixture is adjusted to an optimal temperature range, of about 100-150xc2x0 C., and preferably between about 110-120xc2x0 C. It has been found, unexpectedly, that the isolation of the phenyl ester salt is improved when the crude reaction mixture is adjusted to this optimal temperature range. At temperatures below the optimal range, the mixture becomes too viscous to handle or separate, while at higher temperature loss of product to centrate or filtrate increases. However, within the optimal temperature range, the solid phenyl ester salt can be recovered economically and in good yields.
If the temperature is adjusted batch-wise to the optimal temperature range, by cooling, the cooling step may be effected by methods known in the art. Examples of such methods include removal of heat via an external jacket using a circulation fluid which is colder that the reactor, use of internal coils inside the reactor with a similar media, and/or adiabatic evaporation of the solvent.
Crystals of molecules of large molecular weight and geometric complexity normally grow very slowly. Hence, the rate of cooling must be carefully controlled to avoid supersaturation of the solution that leads to formation of fine crystals, poor crystal shape or inclusion of mother liquor, or co-precipitation of impurities. To avoid these unwanted events a rate of cooling of about 5 to about 15xc2x0 C. is generally acceptable. Preferably the cooling rate will be about 7 to about 12xc2x0 C./hr.
Further, if a mixture or slurry containing a phenyl ester salt and a solvent is at temperature below the optimal temperature range, the mixture may be adjusted, e.g. by heating, to bring the mixture within the optimal temperature range. In this situation, another solvent or additional sulfolane may optionally be added to the mixture or slurry prior to the heating step.
One factor that must be considered in all isolations is the presence of impurities in the crystallization mixture. It is well known that impurities may change both the solubility and the nature of the crystals, as well the viscosity and density of the solvent and thus their ability to be filtered or centrifuged. In general, minimizing the amount of impurities improves the ability to filter or centrifuge. Contaminants may include unreacted starting material, or undesired byproducts. For instance, centrifugation is often hampered by low conversion of starting material, which results in a higher proportion of impurities. For a laboratory-scale reaction, the conversion is generally better controlled and consequently the separation results were normally better than what was experienced in a large-scale pilot plant.
The concentration of the phenyl ester salt in the mixture or slurry fed to the isolation device is preferably in the range of about 18-25 weight percent, although much wider concentration ranges, in the range of from about 10 to about 40 weight percent of solids are within the scope of the invention. If a crude reaction mixture is used, solvent may optionally be added to bring the concentration of the phenyl ester salt to the desired concentration. However, the temperature of the mixture comprising the phenyl ester salt should be adjusted or maintained within the optimal temperature range.
The step wherein the solid phenyl ester salt is separated from the mixture should be carried out while maintaining the temperature of the mixture within the optimal temperature range, of about 100-150xc2x0 C. The separating step may be carried out by any method known in the art, including but not limited to, filtration and centrifugation.
If filtering is used, the filter should be preheated to the optimal temperature range and well insulated to avoid temperature loss during the filtration. Further, for large applications, the filtering process can be effected in batch or continuous mode. The filter media should be selected to withstand the temperature requirements, provide sufficient wettability, avoid chemical degradation, and provide fast filtration with good yields. The pore size of the media must be selected only after the crystal size distribution is available. Examples of batch filters include but are not limited to a pressure nutsche, a vacuum nutsche, a plate and frame filter press, and an auto-filter dryer. The continuous equipment examples include a rotary vacuum filter, a rotary pressure filter, a candle filter, and a belt filter. In each of these applications it is advantageous to prewet the filter media with hot sulfolane. Since filtration rate decreases with increasing cake thickness, careful control of the cake depth is necessary. Production of large lumps during discharge of the cake from the filter causes unnecessary difficulties in further processing. To avoid this, the cake should be discharged while hot.
When centrifugation is used to isolate the phenyl ester salt, the centrifugation mechanism employed can be either a sedimentation centrifuge or a filtration centrifuge. In a filtering centrifuge, the cake is produced on a perforate basket that allows the mother liquor to flow through the perforations, in a manner similar to cake filtration. Here, however, the centrifugal force is the driving force for separation. Sedimentation style centrifuges depend on the differences in density between the solids and the liquid to provide a means to settle the solids. The solids or the liquid can then be removed to obtain the other phase.
Regardless of the type of centrifuge used, the unit should optimally be preheated to the desired temperature and maintained at this temperature during the entire process. For filtering style centrifuges, prewetting of the filter media with sulfolane is desirable, but not necessary. Centrifugation can be performed in either a batch wise or continuous manner. Batch centrifuges have limited capacity in solids collection. Examples of filtering batch centrifuges that could be used to isolate phenyl ester salts include a vertical or horizontal basket centrifuge and an inverting basket centrifuge. Continuous filtering centrifuges usually have stricter requirements in terms of crystal size. Examples of these centrifuges include a pusher and a screen-bowl centrifuge. Sedimentation style centrifuges can operate in batch or continuous mode as well. Examples of the former include the tubular bowl and the disc centrifuge, while examples of the later include the opening bowl disc stack and the solid-bowl continuous-scroll decanter. Here the batch centrifuges provide more flexibility in residence times and g-force whereas the continuous units provide much greater capacity and are much less labor intensive. Regardless of the device used, it must optimally be designed to allow operation within the desired temperature range with little ambient heat loss. The ability to flush with fresh solvent may also be desirable.
It has also been found that the addition of a solvent to a mixture comprising a phenyl ester salt and sulfolane will reduce the viscosity and/or density of the mixture, when the density or viscosity of the solvent added is lower than that of sulfolane. For example, a density of less than about 1.20 g/cm3 at 100xc2x0 C. or a viscosity of less than about 2.56 centipoise at 100xc2x0 C. is required. Additionally, this solvent should be selected such that is not reactive with any of the components in the reaction mixture, does not hydrolyze the product, and has a density and viscosity lower than sulfolane. Suitable solvents may be selected from a variety of acids, alkanes, ketones, alcohols, and other organic acids. Preferred solvents are propionic acid, pentanol, n-butyl alcohol, methylpropyl ketone, methyl isobutyl ketone, methyl isopropyl ketone, and heptane. The preferred boiling point of the solvent is above 90xc2x0 C., and more preferably the boiling point of the solvent is above 100xc2x0 C.
Exemplary solvents used in this step, include a variety carboxylic acids. Acceptable forms of the carboxylic acid, include aqueous solutions of the acid, and concentrated/glacial forms of the acid. According to the process described in this invention, it has been observed that the addition of acid to the reaction mixture improves handling characteristics such as filterability or centrifugeability, which results in improved isolation of the phenyl ester salt.
In a highly preferred embodiment, acetic acid is used. The acid appears to reduce the viscosity and density of the mixture. The amount of acid added to the mixture comprising the phenyl ester salt and sulfolane should generally be below about 10% and preferably between about 2% and about 4%, based upon the weight of the reaction mixture. The addition of excessive amounts of acid should be avoided, as this may lead to decomposition of the phenyl ester salt, resulting in lower yields.
The acetic acid should be added at a temperature at which decomposition is unlikely to occur. For example, in the production of sodium 4-sulfophenyl 6-[(1-oxynonyl)-amino]hexanoate, if the acid is added at temperatures above 150xc2x0 C., there is observed a significant amount of decomposition. Because many of the other phenyl ester salts in the art contain functionality such as ester or amide groups, decomposition at higher temperatures under acidic conditions may also be a concern. Preferably, this step is carried out while maintaining the temperature of the reaction mixture within the optimal temperature range of about 100-150xc2x0 C.
To avoid decomposition of the product, it is necessary to isolate the phenyl ester salt prior to any substantial decomposition of the phenyl ester salt. Therefore, the acetic acid may optionally be added immediately prior to the collecting step, in order to avoid loss of yield due to degradation of product over prolonged times. Typically, the product is collected within about an hour of the addition of the acetic acid.
The step of separating the solid phenyl ester salt from the mixture may be accomplished by the methods discussed previously, such as filtration or centrifugation. This step is carried out while maintaining the temperature of the mixture comprising the phenyl ester salt and sulfolane within the optimal temperature range.
It has also been found that the isolation of a phenyl ester salt from a mixture may be improved by controlling the rate at which the reaction mixture is cooled during crystallization. For instance, the isolation of phenyl ester salts from reaction mixtures is difficult when the product is in the form of fine crystals. To aid in the separation, the cooling of the crude reaction mixture to the separation temperature should be controlled to allow maximum growth of the crystals. If the reaction mixture is cooled too rapidly, small crystals are formed which can blind the filter or centrifuge. Accordingly, the cooling of the mixture should be as slow as is consistent with good economics. For batch processes this is done by reducing the rate at which the temperature is lowered in the vessel. In order to cool the mixture xe2x80x9cslowerxe2x80x9d in continuous processes, the residence time in the vessels must be increased by increasing the number of stages or increasing the vessel size.
Each of the embodiments of the processes described by this invention may be used individually or in combination, to improve the isolation of a phenyl ester salt.
In a particularly preferred embodiment, this invention relates to processes to improve the isolation of phenyl ester salts including sodium 4-sulfophenyl-6-[(1-oxynonyl)amino]hexanoate, sodium 4-(nonanoyloxy) benzenesulfonate, or sodium benzoyloxy benzenesulphonate. Although, as discussed above, the processes of this invention may be used to improve the isolation of a broad range of phenyl ester salts.